White Matter Microstructural Abnormalities Research Articles

Imaging Parameters of the Ipsilateral Medial Geniculate Body May Predict Prognosis of Patients with Idiopathic Unilateral Sudden Sensorineural Hearing Loss on the Basis of Diffusion Spectrum Imaging.

Idiopathic sudden sensorineural hearing loss is an acute unexplained onset of hearing loss. We examined the central auditory pathway abnormalities in patients with unilateral idiopathic sudden sensorineural hearing loss using diffusion spectrum imaging and the relationships between hearing recovery and diffusion spectrum imaging parameters. Forty-eight patients with unilateral idiopathic sudden sensorineural hearing loss with a duration of ≤2 weeks (range, 8.9 ± 4.3 days) and 20 healthy subjects underwent diffusion spectrum imaging tractography. Hearing levels were evaluated using a pure-tone average at initial presentation and 3-month follow-up. Clinical characteristics and MR imaging findings were assessed. Compared with healthy control subjects, the generalized fractional anisotropy values of patients decreased significantly in the bilateral posterior limbs of the internal capsule, with no differences between the ipsilateral and contralateral sides. The quantitative anisotropy values decreased in the Brodmann area 41, contralateral medial geniculate body, bilateral lateral lemniscus, anterior limb of internal capsule, middle temporal gyrus, and anterior corona radiata. Furthermore, at 3-month follow-up, 14 patients had <15 dB of hearing gain. Receiver operating characteristic curve analysis demonstrated that generalized fractional anisotropy in the ipsilateral medial geniculate body was related to prognosis (sensitivity = 64.7%; specificity = 85.7%; area under the curve = 0.796, 95% CI, 0.661-0.931; P < .01). Diffusion spectrum imaging can detect abnormalities of white matter microstructure along the central auditory pathway in patients with unilateral idiopathic sudden sensorineural hearing loss. The generalized fractional anisotropy value of the ipsilateral medial geniculate body may help to predict recovery outcomes.

Childhood conduct problems are associated with reduced white matter fibre density and morphology

Childhood conduct problems are an important public health issue as these children are at-risk of adverse outcomes. Studies using diffusion Magnetic Resonance Imaging (dMRI) have found that conduct problems in adults are characterised by abnormal white-matter microstructure within a range of white matter pathways underpinning socio-emotional processing, while evidence within children and adolescents has been less conclusive based on non-specific diffusion tensor imaging metrics. Fixel-based analysis (FBA) provides measures of fibre density and morphology that are more sensitive to developmental changes in white matter microstructure. The current study used FBA to investigate whether childhood conduct problems were related both cross-sectionally and longitudinally to microstructural alterations within the fornix, inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), and the uncinate fasciculus (UF). dMRI data was obtained for 130 children across two time-points in a community sample with high levels of externalising difficulties (age: time-point 1 = 9.47 – 11.86 years, time-point 2 = 10.67 -13.45 years). Conduct problems were indexed at each time-point using the Conduct Problems subscale of the parent-informant Strengths and Difficulties Questionnaire (SDQ). Conduct problems were related to lower fibre density in the fornix at both time-points, and in the ILF at time-point 2. We also observed lower fibre cross-section in the UF at time-point 1. The change in conduct problems did not predict longitudinal changes in white-matter microstructure across time-points. The current study suggests that childhood conduct problems are related to reduced fibre-specific microstructure within white matter fibre pathways implicated in socio-emotional functioning.

Microstructural white matter abnormalities in obsessive-compulsive disorder: A coordinate-based meta-analysis of diffusion tensor imaging studies.

There are no conclusive diffusion tensor imaging (DTI) findings on obsessive-compulsive disorder (OCD) for now. We conducted a comprehensive meta-analysis of DTI studies to identify white matter (WM) microarchitecture changes in OCD, and also to compare the results differences between the two most frequently used methods (voxel-based analysis, VBA versus tract-based spatial statistics, TBSS) for DTI data. A systematic search was performed on relevant studies that reported fractional anisotropy (FA) alterations between patients with OCD and healthy controls (HC). Seed-based d mapping (SDM) was applied to analyze microstructural WM abnormalities in OCD patients. Subgroup meta-analysis was subsequently performed to explore methodological differences between VBA and TBSS approaches. A total of 30 studies (with 31 datasets) that comprised 855 patients and 875 HC were identified. OCD patients exhibited significantly decreased FA in the right cerebellar hemispheric lobule, corpus callosum (CC), left superior frontal gyrus (orbital part), right gyrus rectus, left superior longitudinal fasciculus and right lenticular nucleus in the pooled meta-analysis. The VBA subgroup showed lower FA in several brain regions while the TBSS subgroup only exhibited significant FA reductions in the CC. According to the pooled meta-analysis, OCD patients presented microstructural abnormalities in distributed WM tracts. However, heterogeneous results were found between VBA and TBSS studies.

Brain Development in Infants of Mothers With Gestational Diabetes Mellitus: A Diffusion Tensor Imaging Study.

The objective of this study was to investigate clinical neurocognitive performance and microstructural white matter (WM) alterations in infants of mothers with gestational diabetes mellitus (GDM) using diffusion tensor imaging. Infants (corrected gestational age, 33.42-36.00 weeks) of mothers with GDM (n = 31) and gestational age- and sex-matched unexposed controls (n = 31) accomplished 3-T diffusion tensor imaging scans and neurocognitive tests. Diffusion tensor imaging measures, mainly referring to fractional anisotropy (FA) values, were compared between 2 groups, and within-group analysis of correlation between FA values and neurocognitive testing outcomes in GDM-exposed infants was conducted subsequently. Fractional anisotropy was significantly decreased in the splenium of corpus callosum, posterior limb of internal capsule, thalamus in infants of mothers with GDM when compared with controls (P < 0.05), reflecting microstructural WM abnormalities in the GDM group. Decreased FA was associated with worse neurocognitive performance in the exposed group (P < 0.05). Individuals of mothers with GDM showed microstructural WM abnormalities in different brain regions, which were significantly related to worse neurocognitive performance. This might reveal that GDM directly insults the brain development of the offspring.

Abnormal white matter microstructure along the thalamus fiber pathways in women with primary dysmenorrhea.

Primary dysmenorrhea (PDM) is a cyclic menstrual pain in the absence of pelvic anomalies, and women with PDM have an increased sensitivity to pain than the internal and external areas associated with menstrual pain. However, the brain abnormality in the ascending pain pathways in dysmenorrhea remains largely unclear. As the thalamus plays a significant role in transmission of nociceptive input, we examined whether white matter microstructure of the thalamus-related fiber tracts obtained by DTI in women with PDM (n= 47) differs from healthy controls. A novel tractography atlas-based analysis method that detects tract integrity and altered microstructural properties along selected fibers was employed. The fiber bundles of interest contained the thalamus- primary somatosensory cortex (SI), thalamus- dorsal anterior cingulate cortex (dACC)/supplementary motor area (SMA), thalamus-insula, and thalamus-ACC. As compared with controls, abnormal white matter microstructures were found along the thalamus-related white matter fiber tracts. Additionally, the intensity of menstrual pain was significantly associated with diffusion measures of thalamus-SI fiber connections. Our study suggested that the thalamus-related pain processing pathways had altered white matter integrity that persisted beyond the time of menstruation, and the white matter microstructure of the thalamus-SI pathways was closely related to menstrual pain in the intensity by women with PDM.

Depression and anxiety mediate the relationship between frontotemporal white matter integrity and quality of life in distressed young adults

Depression and anxiety have been linked to poor quality of life (QoL) – one's subjective perception of relationships, physical health, daily functioning, general sense of well-being and life satisfaction. Elucidating abnormal white matter microstructure associated with mood and other symptoms and QoL is important to facilitate treatment. Ninety-six young adults (18–25 years old) seeking help for psychological distress, irrespective of presence or absence of psychiatric diagnosis completed diffusion weighted and anatomical scans, clinical and behavioral measures, and QoL assessment. We examined relationships between diffusion imaging properties in major white matter tracts involved in emotion processing and regulation, symptoms, and QoL. Depression and general distress levels fully mediated the relationship between fractional anisotropy (FA), an indirect index of fiber collinearity, and radial diffusivity (RD), an index sensitive to axonal/myelin damage, in right uncinate fasciculus and QoL. The relationship between reduced FA (and increased RD) in right uncinate fasciculus and poor QoL was explained by greater severity of depression and general distress. These findings underscore the role of white matter microstructure in right uncinate fasciculus in relation to depressive and general distress symptoms and, in turn, QoL. Importantly, they suggest that measures of white matter microstructure in this tract can be used as putative objective markers of emotion dysregulation, to inform and monitor the impact of interventions to reduce affective symptoms and improve QoL in young adults.

White Matter Microstructural Abnormalities in the Broca's-Wernicke's-Putamen "Hoffman Hallucination Circuit" and Auditory Transcallosal Fibers in First-Episode Psychosis With Auditory Hallucinations.

Functional connectivity abnormalities between Broca's and Wernicke's areas and the putamen revealed by functional magnetic resonance imaging (fMRI) are related to auditory hallucinations (AH). In long-term schizophrenia, reduced white matter structural integrity revealed by diffusion imaging in left arcuate fasciculus (connecting Broca's and Wernicke's areas) is likely related to AH. The structural integrity of connections with putamen and their relation to AH are unknown. Little is known about this relationship in first-episode psychosis (FEP), although auditory transcallosal connections were reported to play a role. White matter in the Broca's-Wernicke's-putamen language-related circuit and auditory transcallosal fibers was examined to investigate associations with AH in FEP. White matter connectivity was measured in 40 FEP and 32 matched HC using generalized fractional anisotropy (gFA) derived from diffusion spectrum imaging (DSI). FEP and HC did not differ in gFA in any fiber bundle. In FEP, AH severity was significantly inversely related to gFA in auditory transcallosal fibers and left arcuate fasciculus. Although the right hemisphere arcuate fasciculus-AH association did not attain significance, the left and right arcuate fasciculus associations were not significantly different. Despite overall normal gFA in FEP, AH severity was significantly related to gFA in transcallosal auditory fibers and the left hemisphere connection between Broca's and Wernicke's areas. Other bilateral tracts' gFA were weakly associated with AH. At the first psychotic episode, AH are more robustly associated with left hemisphere arcuate fasciculus and interhemispheric auditory fibers microstructural deficits, likely reflecting mistiming of information flow between language-related cortical centers.

Micro-structural white matter abnormalities and cognitive impairment in asymptomatic carotid plaque patients: A DTI study using TBSS analysis

BackgroundIt has been shown that symptomatic or severe carotid atherosclerosis is closely related to cognitive impairment and brain white matter damage. However, there is still a lack of effective and non-invasive imaging biomarkers to identify early high-risk cerebrovascular diseases. Therefore, the purpose of this study is to explore the integrity of brain white matter and cognitive impairment in patients with asymptomatic carotid plaques by using imaging technology. MethodsAll subjects were from a project of Stroke Risk Screening and Prevention and were defined as stroke high-risk patients (with three or more stroke risk factors). Tract-based spatial statistics (TBSS) based on diffusion tensor imaging (DTI) was used to analyze the whole brain white matter abnormalities in 61 patients with carotid artery plaque and in 40 healthy controls. At the same time, the general clinical data between the two groups were compared, such as age, gender, smoking, hypertension and cognitive function scores etc. Furthermore, the plaque group was divided into the have-hyperintensities group and the no-hyperintensities group to compare their microstructure of white matter injuries. ResultsThe cognitive scores of plaque group were significantly lower than that of control group. We found that when plaque group and control group were compared, no white matter fiber tracts with difference was found in FA, MD, AD and RD. However, the decrease of FA and the increase of RD were found in some white matter regions (P < 0.05) when comparing the have-hyperintensities group and the no-hyperintensities group. These white matter regions included anterior thalamic radiation, corticospinal tract, cingulum (cingulate gyrus), forceps minor, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, uncinate fasciculus. What’s more, there were significant differences in blood pressure between the two groups. ConclusionThe cognitive function of patients with early high-risk cerebrovascular diseases (asymptomatic carotid plaques) has a downward trend. TBSS based on DTI can help to find out the actual damage of brain white matter in patients with early carotid plaque, and reflect the early pathological changes from the micro level.

Microstructural white matter abnormalities in hypothyroidism evaluation with diffusion tensor imaging tract-based spatial statistical analysis.

Hypothyroidism is presented in a wide range from neuropsychiatric problems including depression, memory and cognitive disorders to poor motor coordination. Against the background of morphologic, functional and molecular changes on the white and grey matter of the brain, we aimed to investigate the effects of hypothyroidism on white matter (WM) integrity using tract-based spatial statistics (TBSS). Eighteen patients with hyperthyroidism and 14 age-sex-matched healthy control subjects were included in this study. TBSS was used in the diffusion tensor imaging study for whole-brain voxel wise analysis of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) of WM. When compared to the control group, the whole brain TBSS revealed extensive reductions of FA in the supratentorial WM including corticospinal tract, posterior limb of the internal capsule (PLIC), uncinate fasciculus, inferior longitudinal fasciculus (p < 0.005). The ROI analyses showed RD increment of superior longitudinal fasciculus, AD decrement of cingulum (CIN), external capsule, PLIC and corpus callosum (CC) in patients with hypothyroidism (p < 0.005). Autoimmune and non-autoimmune hypothyroidism patient subgroups showed a significant difference in terms of hippocampus FA, CIN MD, CC MD, CC AD, CIN RD, SLF RD, CC RD (p < 0.005). CIN FA values showed a negative correlation with the Beck Depression Inventory (p = 0.007, r = - 852). These preliminary results of TBSS analyses represented FA and AD decrement, and RD increment in several WM tracts and indicates the demyelination process underlying pathophysiology of clinical aspects of hypothyroidism.

M155. RECIPROCAL CHANGES IN WHITE MATTER MICROSTRUCTURE IN 22Q11.2 DELETION AND DUPLICATION SYNDROME

BackgroundThe 22q11.2 deletion syndrome is a neurogenetic disorder that is associated with both physical anomalies and neurocognitive impairments. Deletion carriers have a greatly elevated risk of developing schizophrenia (SCZ); as such, it offers a compelling ‘high-penetrance’ model to explore the neuropathology of SCZ risk. Indeed, widespread structural alterations of both gray and white matter have been reported for 22q11.2 deletion carriers.Interestingly, there are also cases of duplications at the same gene locus. While less is known about the phenotype associated with 22q11.2 duplication, carriers also present physical and neurodevelopmental abnormalities, although they may have reduced risk of developing SCZ compared to the general population. The only study to date which looked at brain structure in duplication carriers found reciprocal effects of 22q11.2 deletion and duplication on cortical thickness and surface measurements.In the present study, we apply diffusion magnetic resonance imaging (MRI) to examine the white matter microstructure in both 22q11.2 deletion and duplication carriers.MethodsMulti-shell diffusion-weighted images were acquired on a 3 Tesla MRI scanner from 13 healthy control individuals (HC), 25 deletion carriers, and 18 22q11.2 duplication carriers. Images were preprocessed utilizing the Human Connectome Project (HCP) Minimal Preprocessing Pipeline v4.0.0.Free Water imaging was applied, which differentiates the diffusion signal into a free-water compartment and a tissue compartment. The output parameters are the free-water fractional volume (FW) and a free-water corrected diffusion tensor from which fractional anisotropy of the tissue (FAT) is calculated.We compared FAT and FW maps between 1) HC and 22q11.2 deletion carriers and 2) HC and 22q11.2 duplication carriers using Tract-Based Spatial Statistics (TBSS) and voxel-wise, non-parametric statistics (5000 permutations, threshold-free cluster enhancement, corrected for age and sex).Lastly, white matter clusters that displayed significant differences between 22q11.2 deletion or duplication and HC were extracted. We averaged FAT and FW values over these significant clusters for each individual and correlated with the scores of the Structured Interview for Prodromal Syndromes (SIPS).Results22q11.2 deletion carriers showed significant (p<0.05) FW reductions (72% of white matter skeleton) and FAT increase (8%) when compared to HC. In contrast, 22q11.2 duplication carriers displayed the opposite effect, with significant (p<0.05) widespread FW increase (51%) and FAT decrease (50%) when compared to HC.Both 22q11.2 deletion and duplication carriers scored higher on the SIPS than HC, with negative symptom score differences being the most pronounced (mean for HC= 1.36, mean for 22q11.2 duplication = 7.0, mean for 22q11.2 deletion =9.96, F=6.68, df=2, p<.003).FAT and FW were not associated with SIPS scores in 22q11.2 deletion syndrome. However, FAT was negatively correlated with the negative symptom score in 22q11.2 duplication carriers (Spearman rho=-.61, p<.009).DiscussionWe observed opposing effects of gene-dosage on FAT and FW. While we did not see an association between WM measurements and psychotic symptoms in 22q11.2 deletion, there was an association of WM structure with negative symptoms in 22q11.2 duplication carriers.These findings highlight the importance of studying the influence of reciprocal chromosomal imbalance on white matter architecture. Ongoing longitudinal studies may help advance understanding of the role of microstructural white matter abnormalities in the emergence of neuropsychiatric symptoms.

Abnormalities of effective connectivity and white matter microstructure in the triple network in patients with schizophrenia

Disorganized communication among large-scale brain networks, especially in the salience network, default mode network and central executive network, have been consistently reported in schizophrenia (SZ) patients. However, abnormal patterns of the effective connectivity and abnormalities in the white matter of these networks remains unclear in patients with SZ. Fifty-six SZ patients and fifty-five healthy controls were enrolled in the present study and underwent resting state functional magnetic resonance and diffusion tensor imaging. Twelve main nodes within the triple networks were defined by independent components analysis. Effective connectivity between these main nodes was computed using Granger causality analysis. Voxel-based analysis of the diffusion tensor imaging data was conducted to explore white matter changes. The SZ patients showed abnormal effective connectivity between the anterior cingulate cortex and the dorsolateral prefrontal cortex. The abnormal white matter showed decreased fractional anisotropy localized in the bilateral anterior corona radiate and left superior long fasciculus in patients with SZ. These findings shed light on the importance of the triple network in the pathogenesis of SZ, which may facilitate the understanding of SZ.

State-Independent Microstructural White Matter Abnormalities in Major Depressive Disorder.

BackgroundEven with continuous antidepressant treatment, residual symptoms and the risk of relapse can persist in remitted major depressive disorder (MDD) patients. Hence, having a clear recognition of the persistent abnormalities of the underlying neural substrate in MDD through a longitudinal investigation is of great importance.MethodsA total of 127 adult medication-free MDD patients with an acute depressive episode and 118 matched healthy controls (HCs) underwent diffusion tensor imaging. Over a 6-month treatment course, 62 remitted patients underwent a second scan. Remission was defined as a 24-item Hamilton Depression Rating Scale (HAMD24) score ≤7 for at least two weeks. Diffusion tensor imaging was performed with a 3.0 T scanner. Differences in whole-brain fractional anisotropy (FA) between MDD patients and HCs were assessed by an independent t-test using gender, age, and education as covariates.ResultsSignificant FA reductions in the left insula, left middle occipital gyrus, right thalamus, left pallidum and left precuneus were observed in current MDD (cMDD) patients compared with HCs. Moreover, significant FA reductions in the left insula were observed in remitted (rMDD) patients compared to HCs. However, no significant differences in FA values were found when comparing cMDD and rMDD patients.ConclusionsThe abnormalities in the insula showed state-independent characteristics, while the abnormalities in the middle occipital gyrus, thalamus, pallidum and precuneus seemed to be state-dependent impairments in MDD patients.

Evidence of Neural Microstructure Abnormalities in Type I Chiari Malformation: Associations Among Fiber Tract Integrity, Pain, and Cognitive Dysfunction.

Previous case-control investigations of type I Chiari malformation (CMI) have reported cognitive deficits and microstructural white matter abnormalities, as measured by diffusion tensor imaging (DTI). CMI is also typically associated with pain, including occipital headache, but the relationship between pain symptoms and microstructure is not known. Eighteen CMI patients and 18 adult age- and education-matched control participants underwent DTI, were tested using digit symbol coding and digit span tasks, and completed a self-report measure of chronic pain. Tissue microstructure indices were used to examine microstructural abnormalities in CMI as compared with healthy controls. Group differences in DTI parameters were then reassessed after controlling for self-reported pain. Finally, DTI parameters were correlated with performance on the digit symbol coding and digit span tasks within each group. CMI patients exhibited greater fractional anisotropy (FA), lower radial diffusivity, and lower mean diffusivity in multiple brain regions compared with controls in diffuse white matter regions. Group differences no longer existed after controlling for self-reported pain. A significant correlation between FA and the Repeatable Battery for the Assessment of Neuropsychological Status coding performance was observed for controls but not for the CMI group. Diffuse microstructural abnormalities appear to be a feature of CMI, manifesting predominantly as greater FA and less diffusivity on DTI sequences. These white matter changes are associated with the subjective pain experience of CMI patients and may reflect reactivity to neuroinflammatory responses. However, this hypothesis will require further deliberate testing in future studies.

Multiparametric mapping of white matter microstructure in catatonia

Catatonia is characterized by motor, affective and behavioral abnormalities. To date, the specific role of white matter (WM) abnormalities in schizophrenia spectrum disorders (SSD) patients with catatonia is largely unknown. In this study, diffusion magnetic resonance imaging (dMRI) data were collected from 111 right-handed SSD patients and 28 healthy controls. Catatonic symptoms were examined on the Northoff Catatonia Rating Scale (NCRS). We used whole-brain tract-based spatial statistics (TBSS), tractometry (along tract statistics using TractSeg) and graph analytics (clustering coefficient-CCO, local betweenness centrality-BC) to provide a framework of specific WM microstructural abnormalities underlying catatonia in SSD. Following a categorical approach, post hoc analyses showed differences in fractional anisotrophy (FA) measured via tractometry in the corpus callosum, corticospinal tract and thalamo-premotor tract as well as increased CCO as derived by graph analytics of the right superior parietal cortex (SPC) and left caudate nucleus in catatonic patients (NCRS total score ≥ 3; n = 30) when compared to non-catatonic patients (NCRS total score = 0; n = 29). In catatonic patients according to DSM-IV-TR (n = 43), catatonic symptoms were associated with FA variations(tractometry) of the left corticospinal tract and CCO of the left orbitofrontal cortex, primary motor cortex, supplementary motor area and putamen. This study supports the notion that structural reorganization of WM bundles connecting orbitofrontal/parietal, thalamic and striatal regions contribute to catatonia in SSD patients.

Diffusion Tensor Imaging Studies on Spontaneous Subarachnoid Hemorrhage-Related Brain Injury: A Mini-Review.

Accurate diagnosis of the presence and severity of neural injury in patients with subarachnoid hemorrhage (SAH) is important in neurorehabilitation because it is essential for establishing appropriate therapeutic strategies and developing a prognosis. Diffusion tensor imaging has a unique advantage in the identification of microstructural white matter abnormalities which are not usually detectable on conventional brain magnetic resonance imaging. In this mini-review article, 12 diffusion tensor imaging studies on SAH-related brain injury were reviewed. These studies have demonstrated SAH-related brain injuries in various neural tracts or structures including the cingulum, fornix, hippocampus, dorsolateral prefrontal region, corticospinal tract, mamillothalamic tract, corticoreticular pathway, ascending reticular activating system, Papez circuit, optic radiation, and subcortical white matter. We believe that these reviewed studies provide information that would be helpful in science-based neurorehabilitation of patients with SAH. Furthermore, the results of these reviewed studies would also be useful for clarification of the pathophysiological mechanisms associated with SAH-related brain injury. However, considering the large number of neural tracts or neural structures in the brain, more research on SAH-related brain injury in other neural tracts or structures should be encouraged.

The Relationship Between White Matter Microstructure and General Cognitive Ability in Patients With Schizophrenia and Healthy Participants in the ENIGMA Consortium.

Schizophrenia has recently been associated with widespread white matter microstructural abnormalities, but the functional effects of these abnormalities remain unclear. Widespread heterogeneity of results from studies published to date preclude any definitive characterization of the relationship between white matter and cognitive performance in schizophrenia. Given the relevance of deficits in cognitive function to predicting social and functional outcomes in schizophrenia, the authors carried out a meta-analysis of available data through the ENIGMA Consortium, using a common analysis pipeline, to elucidate the relationship between white matter microstructure and a measure of general cognitive performance, IQ, in patients with schizophrenia and healthy participants. The meta-analysis included 760 patients with schizophrenia and 957 healthy participants from 11 participating ENIGMA Consortium sites. For each site, principal component analysis was used to calculate both a global fractional anisotropy component (gFA) and a fractional anisotropy component for six long association tracts (LA-gFA) previously associated with cognition. Meta-analyses of regression results indicated that gFA accounted for a significant amount of variation in cognition in the full sample (effect size [Hedges' g]=0.27, CI=0.17-0.36), with similar effects sizes observed for both the patient (effect size=0.20, CI=0.05-0.35) and healthy participant groups (effect size=0.32, CI=0.18-0.45). Comparable patterns of association were also observed between LA-gFA and cognition for the full sample (effect size=0.28, CI=0.18-0.37), the patient group (effect size=0.23, CI=0.09-0.38), and the healthy participant group (effect size=0.31, CI=0.18-0.44). This study provides robust evidence that cognitive ability is associated with global structural connectivity, with higher fractional anisotropy associated with higher IQ. This association was independent of diagnosis; while schizophrenia patients tended to have lower fractional anisotropy and lower IQ than healthy participants, the comparable size of effect in each group suggested a more general, rather than disease-specific, pattern of association.

Damage Mechanisms to Oligodendrocytes and White Matter in Central Nervous System Injury: The Australian Context.

Traumatic brain injury (TBI) and spinal cord injury (SCI) present a significant contribution to the global disease burden. White matter tracts are susceptible to both the physical forces of trauma and cascades of pathological secondary degeneration. Oligodendrocytes, the myelinating cells of the central nervous system (CNS), and their precursors are particularly vulnerable cell populations and their disruption results in a loss of white matter, dysmyelination, and poor myelin repair. White matter aberrations in TBI and SCI can be visualized in vivo using a number of magnetic resonance imaging (MRI)-based modalities. Recent advances in diffusion MRI allow researchers to investigate subtle abnormalities in white matter microstructure and connectivity, resting state networks, and metabolic perturbations associated with injury. Damage to oligodendroglia underlies white matter aberrations and occurs as a result of glutamate excitotoxicity, intracellular calcium ion (Ca2+) overload, and oxidative damage to lipids, proteins, and DNA. Structural changes to myelin include myelin decompaction, loosening of myelin lamellae, and disruption to the node of Ranvier complex. Neuronal and functional loss accompany dysmyelination together with an increase in astro- and microgliosis. Remyelination is often partial, and more work is needed to understand deficits in remyelination post-injury to develop strategies to both protect and repair myelin and thereby preserve function. This review covers disruptions to oligodendrocyte function and white matter tract structure in the context of TBI and SCI, with an emphasis on Australian contributions in recognition of the International Neurotrauma Symposium held in Melbourne, Australia in 2020.

Widespread white matter microstructural abnormalities and cognitive impairment in schizophrenia, bipolar disorder, and major depressive disorder: Tract-based spatial statistics study

Widespread white matter microstructural abnormalities and cognitive impairment in schizophrenia, bipolar disorder, and major depressive disorder: Tract-based spatial statistics study

Systems modeling of white matter microstructural abnormalities in Alzheimer's disease.

Microstructural abnormalities in white matter (WM) are often reported in Alzheimer's disease (AD). However, it is unclear which brain regions have the strongest WM changes in presymptomatic AD and what biological processes underlie WM abnormality during disease progression. We developed a systems biology framework to integrate matched diffusion tensor imaging (DTI), genetic and transcriptomic data to investigate regional vulnerability to AD and identify genetic risk factors and gene subnetworks underlying WM abnormality in AD. We quantified regional WM abnormality and identified most vulnerable brain regions. A SNP rs2203712 in CELF1 was most significantly associated with several DTI-derived features in the hippocampus, the top ranked brain region. An immune response gene subnetwork in the blood was most correlated with DTI features across all the brain regions. Incorporation of image analysis with gene network analysis enhances our understanding of disease progression and facilitates identification of novel therapeutic strategies for AD.

Differentiation of Early Alzheimer's Disease, Mild Cognitive Impairment, and Cognitively Healthy Elderly Samples Using Multimodal Neuroimaging Indices

Brain resting-state functional connectivity (rsFC), white matter (WM) integrity, and cortical morphometry, as well as neuropsychological performance, have seldom been studied together to differentiate Alzheimer's disease (AD), mild cognitive impairment (MCI), and elderly cognitively healthy comparison (eCHC) samples in the context of the same study. We examined brain rsFC in samples of patients with mild AD (n = 50) and MCI (n = 49) in comparison with eCHC samples (n = 48) and then explored whether rsFC abnormalities can be linked to underlying gray matter (GM) volumetric and/or WM microstructural abnormalities. The mild AD sample showed significantly increased rsFC in the executive control network (ECN) and dorsal attention network (DAN) compared with the eCHC sample, and increased rsFC in ECN compared with MCI. Brain regions corresponding to both these resting-state networks (RSNs) showed significant reduction in fractional anisotropy in mild AD in comparison with eCHC. Significant GM volumetric reductions were observed in brain regions corresponding to both RSNs in the mild AD sample compared with MCI as well as eCHC samples. The association of default mode network-DAN anticorrelation with cognitive performances differentiated mild AD and MCI from eCHC sample. These findings highlight the association between brain structural and functional abnormalities as well as cognitive impairment that enables differentiation between early AD, MCI, and eCHC samples.